title: Molecular and cellular basis of obsessive-compulsive disorder-like behaviors: emerging view from mouse models.
abstract: OBJECTIVE
  This article reviews recent literature describing novel mouse genetic models of obsessive-compulsive disorder-like behaviors and neurobiological insights gained from analyses of such models.
  
  
  RESULTS
  Obsessive-compulsive disorder is a common neuropsychiatric disorder characterized by recurrent intrusive thoughts (obsessions) and ritualistic (compulsive) behaviors. Although the cause of this disorder remains unclear, recent studies of novel mouse genetic models with excessive grooming behaviors have begun to shed light on the molecular and cellular mechanisms underlying the pathogenesis of 'obsessive-compulsive disorder-like' behaviors. Genetic deletion of three genes in mice, Hoxb8, Sapap3, and Slitrk5, leads to pathological behaviors including adult-onset excessive grooming with mild-to-severe hair loss and self-injury. In two of the models, the Sapap3-deficient and the Slitrk5-deficient mice, the abnormal grooming behaviors are associated with enhanced anxiety and these pathological behaviors can be curtailed with subchronic administration of a selective serotonin reuptake inhibitor, suggesting the predictive validity of such models. Molecular, pathophysiological, and genetic analyses of these models reveal several insights on the etiological basis of abnormal behaviors in these mice, including abnormal cortico-striatal synapse formation and function in Sapap3 mice, impaired development and function of bone marrow-derived microglia in Hoxb8 mice, and abnormal striatal neuronal differentiation and neurotransmission in Slitrk5 mice.
  
  
  CONCLUSIONS
  Novel animal models provide powerful tools to investigate the molecular, cellular, and circuitry mechanisms of obsessive-compulsive disorder-like behaviors. Detailed analyses of these models may provide candidate molecules and mechanisms for the investigation of cause and therapy of obsessive-compulsive disorder.
authors.affiliation: Center for Neurobehavioral Genetics, Semel Institute for Neuroscience & Human Behavior, Department of Psychiatry & Biobehavioral Sciences, Brain Research Institute, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA. xwyang@mednet.ucla.edu
authors.forename: X William
authors.initials: XW
authors.lastname: Yang
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Lu
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D003192:Compulsive Behavior / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology; D004195:Disease Models, Animal; D006120:Grooming / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D017628:Microglia / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics; D009771:Obsessive-Compulsive Disorder / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology
chemical_list: D018398:Homeodomain Proteins; C095822:Hoxb8 protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C523020:Sapap3 protein, mouse; C550141:Slitrk5 protein, mouse